The PDLCs were pre-treated with Wnt5a siRNA (30 nM) or Wnt5 peptide (500 ng/mL) for 2 hours, post-incubated with Tβ4 peptide (1 μg/mL) and 200 μM H2O2 for 48 hours (A-E), and then conditioned medium (CM) was collected. The bar graph shows the fold increase in protein or mRNA expression compared with control. * Statistically significant differences compared with the control, p<0.05. # Statistically significant difference compared with the H2O2-treated group. The data presented were representative of three independent experiments.
About three months after quitting, I did have a major relapse, which was falling back into old habits for about two weeks. And the whole time I knew what was happening, I knew how dangerous it was, but I couldn't stop myself. I felt like I couldn't connect to anyone without drinking. I couldn't talk to my friends, I couldn't be open and honest with anybody in my life without already having had a few drinks. It was a really disconnected, really unpleasant feeling. That's what I couldn't sit with and I couldn't cope with that feeling, so I went back to drinking.
Horvath, G. A., Stockler-Ipsiroglu, S. G., Salvarinova-Zivkovic, R., Lillquist, Y. P., Connolly, M., Hyland, K., Blau, N., Rupar, T., and Waters, P. J. Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms. Mol.Genet.Metab 2008;94(1):127-131. View abstract.
In addition to its intracellular role as the major actin-sequestering molecule in cells of many multicellular animals, thymosin β4 shows a remarkably diverse range of effects when present in the fluid surrounding animal tissue cells. Taken together, these effects suggest that thymosin has a general role in tissue regeneration. This has suggested a variety of possible therapeutic applications, and several have now been extended to animal models and human clinical trials.
Evidence for this role of oxytocin come from two types of experiments. First, infusion of oxytocin into the ventricles of the brain of virgin rats or non-pregnant sheep rapidly induces maternal behavior. Second, administration into the brain of antibodies that neutralize oxytocin or of oxytocin antagonists will prevent mother rats from accepting their pups. Other studies support the contention that this behavioral effect of oxytocin is broadly applicable among mammals.
To determine whether MAPK and NF-κB signaling pathways were involved in the anti-osteoclastogenic function of Tβ4, the effect of Tβ4 peptide on the phosphorylation levels of ERK, JNK, and p38 MAPK(s) as well as the nuclear translocation of NF-κB p65 in RANKL-stimulated BMMs were examined. As shown in Fig 8B, Tβ4 peptide inhibited the RANKL-induced phosphorylation of p38, ERK, and JNK and nuclear translocation of NF-κB p65.
The polyherbal formula described for acute wounds promoted both angiogenesis and fibroblast proliferation and collagen synthesis in a streptozotocin diabetic rat model (Gupta et al., 2008). Dressings impregnated with copper oxide applied to wounds of diabetic mice resulted in the upregulation of the pro-angiogenic factors placental growth factor, hypoxia-inducible factor-1α and VEGF, leading to increased angiogenesis and faster wound closure (Borkow et al., 2010). High-throughput screening of medicinal plants known to be beneficial for blood circulation identified a material named SBD.4a from the plant Angelica sinensis as having angiogenic properties on a par with PDGF-BB (Zhao et al., 2006).
In humans, 5-HTP is the nutrient precursor to the neurotransmitter serotonin – widely known as the 'happy neurotransmitter' – meaning 5-HTP converts directly into serotonin in the brain. As well as being in our bodies, it's found naturally in the seeds of a woody shrub native to West Africa. By taking it as a supplement, in theory, you will end up with more serotonin in your brain. Serotonin deficiency is linked to depression, anxiety and a whole host of physical and mental ailments. Raising its levels seems to help brain cells send and receive chemical messages, which in turn boosts mood.
Jump up ^ Wermter AK, Kamp-Becker I, Hesse P, Schulte-Körne G, Strauch K, Remschmidt H (March 2010). "Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level". American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 153B (2): 629–39. doi:10.1002/ajmg.b.31032. PMID 19777562.
On a personal note, 5-HTP is actually one of the 1st nootropics I ever used. When I was a teenager and would go to raves me and my friends would use 5-HTP the next day because ecstasy (MDMA) diminishes the serotonin levels. Anyone with much experience with ecstasy knows that the day(s) after can be pretty hellish because the drug so depletes your feel good neurotransmitters, 5-HTP is sort of a Biohack for this.
Ive been struggling with my left brachialis and so after listening to a podcast in which you mentioned BPC-157 I tried it out. I was hoping for a miracle cure, which I did not get. However, I believe it certainly helped a lot. I am considering a second round. But the peptide rabbit hole is certainly interesting and I am most keen to try some others. But I would like to see if you have some advise for me on another topic. After having listened to your podcast with Dr Gains I thought that either you or Dr Gains may be able to at least point me in the right direction. My wife suffers from a condition called Pelvic Vein Congestion which causes her a lot of pain. From what I understand, she has a seemingly unnatural mass of veins around her uterus which may also suffer from a “valve” type problem in which blood can potentially run in the opposite direction and pool in locations which causes pain. She has been to doctors which offer invasive solutions with unattractive success rates. I have been searching for other cures, but the only thing that I found (supplement with Diosmin and Hisperidan) had some psychological effects. Any thoughts?
A: While it is possible there is an interaction, it most likely is not severe or life-threatening. Keep in mind that the "T" in HTP stands for tryptophane, which is an essential amino acid that your body processes routinely. The most common interaction involved with 5-HTP is with antidepressants or other medications that are intended to affect brain chemistry, as 5-HTP is converted into serotonin, an important brain chemical that helps regulate mood.
Toxicity effects of melanotan II from therapeutic and overdose exposures include renal dysfunction, rhabdomyolysis, sympathomimetic overdrive, change in size and pigmentation of pre-existing moles, rapid increase in the number of new moles, associated with causing melanomas, posterior reversible encephalopathy syndrome, refractory priapism, stretching and yawning syndrome, shortness of breath, chest pain, abdominal cramping and pain, dizziness and lethargy.
Froemke's and Tsien's work fits into a broader theory: that one way oxytocin helps social interaction and recognition is by enhancing the brain's response to socially relevant sights, sounds or other stimuli. Young has shown that the hormone helps mice to recognize and pay attention to the smells of other mice7; others found that it promotes people's ability to recognize faces8.
In addition, in the Phase 1 clinical trial in healthy volunteers using a randomised, double-blind, placebo-controlled single- and multiple-dose Phase 1 clinical trial, the safety and pharmacokinetics of the intravenous administration of TB-4 was evaluated. From this, intravenous administration of TB-4 appears to be safe and well-tolerated by all subjects with no dose limiting toxicity or serious adverse events reported.
Because of its role in creating serotonin, 5-HTP is indirectly involved in producing melatonin, a hormone that is critical for sleep. Melatonin helps the body’s bio clock stay in sync, and regulates daily sleep-wake cycles. A strong bio clock and regular sleep-wake routines are the cornerstone of healthy, restful, rejuvenating sleep. Research suggests that 5-HTP may help shorten the time it takes to fall asleep and increase sleep amounts.
Wonderful column. My expertise is the psychology of risk perception, and I have done some reading on oxytocin and trust (not the kind you want to boost in a bar with Liquid Trust – you can the stuff with pheromones – to boost THAT kind of trust). It turns out there is a high concentration of oxytocin receptors on the amygdala, the area of the brain where fear starts. As oxytocin levels go up, the ability of the amygdala to be warry and more mistrustful goes down. I describe this in Ch. 3 of How Risky Is It, Really? Why Our Fears Don’t Always Match the Facts. A few graphs of which are below. I wonder whether the influence of oxytocin on the amygdala might be connected with the finding of the study you write about.
I found this to be an excellent supplement for myself, which overcomes the rate limiting step when the body converts tryptophan to 5-HTP. I am sleeping much better and handling life's normal stresses better. If you haven't already, become familiar with how/why the body converts L-Tryptophan > 5-HTP > Serotonin > Melatonin. Very interesting! Thank you Bulk Nutrients for making this available.
One study investigating romantic stress that looked at nondepressed youth who went through a recent breakup and were given 60mg of Griffonica Simplicifonia (12.8mg 5-HTP) twice a day for 6 weeks in an open-label study noted reductions in percieved romantic stress when measured at the 3 week mark with no further improvement at 6 weeks; there was no control nor placebo group in this study.
Melanotan II non-selectively mimics the action of melanocortin peptides. These are natural hormones involved with pigmentation, energy homeostasis, sexual functioning, the immune system, inflammation, and the cardiovascular system. Much like melanotan I (afamelanotide), melanotan II stimulates the production of eumelanin, causing the skin to go darker (tanning).
Both the production of oxytocin and response to oxytocin are modulated by circulating levels of sex steroids. The burst of oxytocin released at birth seems to be triggered in part by cervical and vaginal stimulation by the fetus, but also because of abruptly declining concentrations of progesterone. Another well-studied effect of steroid hormones is the marked increase in synthesis of uterine (myometrial) oxytocin receptors late in gestation, resulting from increasing concentrations of circulating estrogen.
RegeneRX Biopharmaceuticals is focusing on the commercialization of Tb4 “For the treatment of injured tissue and non-healing wounds, to enable more rapid repair and/or tissue regeneration.” Especially needy are diabetics who suffer from poor blood circulation and loss of sensation of pain that keeps their wounds unnoticed and unattended for days, leading to ulcers that may not heal. Other hard healing wounds are pressure ulcers in patients who are bed ridden and often receive skin grafts as treatment, or reconstructive surgery.
Oxytocin has been shown to help people with autism improve their ability to recognize emotion, and Wallum found that the same receptor variant that increases risk for marital crisis in women is linked to social problems in girls. These include trouble getting along with others and a preference for being alone. This and Feldman’s work on oxytocin’s importance for the mother–child bond suggests that the hormone is more involved in the communication component of love between couples than the romantic component of love.
Treatment with thymosin beta 4 (Tβ4) reduces infarct volume and preserves cardiac function in preclinical models of cardiac ischemic injury. These effects stem in part from decreased infarct size, but additional benefits are likely due to specific antifibrotic and proangiogenic activities. Injected or transgenic Tβ4 increase blood vessel growth in large and small animal models, consistent with Tβ4 converting hibernating myocardium to an actively contractile state following ischemia. Tβ4 and its degradation products have antifibrotic effects in in vitro assays and in animal models of fibrosis not related to cardiac injury. This large number of pleiotropic effects results from Tβ4’s many interactions with cellular signaling pathways, particularly indirect regulation of cellular motility and movement via the SRF–MRTF–G-actin transcriptional pathway. Variation in effects and effect sizes in animal models may potentially be due to variable distribution of Tβ4. Preclinical studies of PK/PD relationships and a reliable pharmacodynamic biomarker would facilitate clinical development of Tβ4.
Oxytocin produces antidepressant-like effects in animal models of depression, and a deficit of it may be involved in the pathophysiology of depression in humans. The antidepressant-like effects of oxytocin are not blocked by a selective antagonist of the oxytocin receptor, suggesting that these effects are not mediated by the oxytocin receptor. In accordance, unlike oxytocin, the selective non-peptide oxytocin receptor agonist WAY-267,464 does not produce antidepressant-like effects, at least in the tail suspension test. In contrast to WAY-267,464, carbetocin, a close analogue of oxytocin and peptide oxytocin receptor agonist, notably does produce antidepressant-like effects in animals. As such, the antidepressant-like effects of oxytocin may be mediated by modulation of a different target, perhaps the vasopressin V1A receptor where oxytocin is known to weakly bind as an agonist.
Animal studies have found high levels of both stress and oxytocin in voles that were separated from other voles. However, when the voles were given doses of oxytocin, their levels of anxiety, cardiac stress, and depression fell, suggesting that stress increases internal production of the hormone, while externally supplied doses can help reduce stress.
Research in the early 1960s showed that in rats, administration of α-MSH caused sexual arousal, and work on this continued in many labs up through the 1980s, when scientists at University of Arizona began attempting to develop α-MSH and analogs as potential sunless tanning agents, and synthesized and tested several analogs, including melanotan-I and melanotan II.
Jump up ^ Venkatesh B, Si-Hoe SL, Murphy D, Brenner S (November 1997). "Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes". Proceedings of the National Academy of Sciences of the United States of America. 94 (23): 12462–6. Bibcode:1997PNAS...9412462V. doi:10.1073/pnas.94.23.12462. PMC 25001. PMID 9356472.
Feeding: a 2012 paper suggested that oxytocin neurons in the para-ventricular hypothalamus in the brain may play a key role in suppressing appetite under normal conditions and that other hypothalamic neurons may trigger eating via inhibition of these oxytocin neurons. This population of oxytocin neurons are absent in Prader-Willi syndrome, a genetic disorder that leads to uncontrollable feeding and obesity, and may play a key role in its pathophysiology.
The structure of oxytocin is very similar to that of vasopressin (cysteine - tyrosine - phenylalanine - glutamine - asparagine - cysteine - proline - arginine - glycine), also a nonapeptide with a sulfur bridge, whose sequence differs from oxytocin by 2 amino acids. A table showing the sequences of members of the vasopressin/oxytocin superfamily and the species expressing them is present in the vasopressin article. Oxytocin and vasopressin were isolated and synthesized by Vincent du Vigneaud in 1953, work for which he received the Nobel Prize in Chemistry in 1955.
Thymosin beta-4 (Tβ4) is a water-soluble, 43-amino acid, and 4.9 kDa protein that was originally isolated from bovine thymus . Since Tβ4 is the major actin-sequestering molecule in eukaryotic cells and is found in all cells , Tβ4 has multiple diverse cellular functions, including tissue development, migration, angiogenesis, and wound healing . We previously reported that Tβ4-overexpressing transgenic mice, using a construct on the skin-specific keratin-5 promoter, have abnormal tooth development and enhanced stimulation of hair growth . Moreover, exogenous Tβ4 has anti-inflammatory effects in the bleomycin-induced mouse model of lung fibrosis , tooth extraction sockets in rats , rat model of myocardial ischemia , corneal wound healing , wound healing of rat palatal mucosa , in vitro model of cultured human gingival fibroblasts , and cardiac fibroblasts . However, the effects of Tβ4 over expression or inhibition on differentiation are controversial. Exogenous β4 peptide inhibited osteogenic differentiation but facilitated adipogenic differentiation in human bone marrow-derived-mesenchymal stem cells (MSCs) . In contrast, Tβ4 inhibition by Tβ4 siRNA attenuated odontoblastic differentiation in the odontoblast-like cells, MDPC-23 . Moreover, we recently demonstrated that odontoblastic differentiation was enhanced by activation of Tβ4 by Tβ4 peptide but was decreased by Tβ4 siRNA in human dental pulp cells (HDPCs) . However, the effects of Tβ4 on osteoclastic differentiation have not been reported.
Wow I wonder if it will help those of us with Ehlers Danlos Syndrome – a collagen disorder that causes ligament laxity and makes those with it prone to easy subluxations and early onset arthritis. I have so many injuries from my daily life due to this disorder. I know this won’t fix my faulty collagen since that is encoded in my genes but perhaps it would help with the symptoms – a bunch of torn ligaments and worn out joints. Thanks for sharing!
When practicing deep breathing, focus on a calmer state of mind as you distract yourself from overwhelming thoughts and sensations. Sit in a quiet area and practice the following: Take a slow, deep breath through your nose, allowing both your stomach and chest to rise. Once your stomach is fully expanded, breathe out through your mouth, just as slowly as when you were breathing in.
Injected oxytocin analogues are used to induce labour and support labour in case of non-progression of parturition. It has largely replaced ergotamine as the principal agent to increase uterine tone in acute postpartum haemorrhage. Oxytocin is also used in veterinary medicine to facilitate birth and to increase milk production. The tocolytic agent atosiban (TractocileÂ®) acts as an antagonist of oxytocin receptors; this drug is registered in many countries to suppress premature labour between 24 and 33 weeks of gestation. It has fewer side-effects than drugs previously used for this purpose (ritodrine, salbutamol and terbutaline).
In December 2010, the delegate made a delegate only decision to include afamelanotide (also known as melanotan I) with a cross-reference to melanocyte stimulating hormone (MSH) for inclusion into the current Poisons Standard. It was noted that afamelanotide should not be confused with a similar substance commonly known as Melanotan-II, which is a cyclic lactam synthetic analogue of α-MSH. It was noted that melanotan-II was under investigation for treating sexual dysfunction, although this has been abandoned due to side effects associated with the immune and cardiovascular systems. Its metabolite, bremelanotide, is under investigation for treating haemorrhagic shock.
Studies of oxytocin also have found that it is an important chemical messenger that controls some human behaviors and social interaction. It is oxytocin that triggers the bond between a mother and an infant, and it may also play a role in recognition, sexual arousal, trust, and anxiety. Some research shows that the hormone may affect addiction and stress as well.
An estimated 1.4 million people sustain traumatic brain injury (TBI) each year in the United States, and more than 5 million people are coping with disabilities from TBI at an annual cost of more than $56 billion.1 There are no commercially-available pharmacological treatment options available for TBI because all clinical trial strategies have failed.2,3 The disappointing clinical trial results may be due to variability in treatment approaches and heterogeneity of the population of TBI patients.4-9 Another important aspect is that most clinical trial strategies have used drugs that target a single pathophysiological mechanism, although many mechanisms are involved in secondary injury after TBI.4 Neuroprotection approaches have historically been dominated by targeting neuron-based injury mechanisms as the primary or even exclusive focus of the neuroprotective strategy.3 In the vast majority of preclinical studies, the treatment compounds are administered early and, frequently, even before TBI.10,11 Clinically, the administration of a compound early may be problematic because of the difficulty in obtaining informed consent.12
Our research mainly focusses on this early social experiences that people have that can be positive or negative, and that can really shape our developing brain. There have been some very interesting studies, for example, with children that grew up in Romanian orphanages. And we know that that early start, where it's really deprived from social contact and physical contact, had a massive impact. So we see that oxytocin levels, for example, are much lower than we would expect in other kids.
“Ultimately you’re body is going to down-regulate the enzymes needed to convert the tyrosine/l-phenylalanine into dopamine and norepinephrine; this also counts for 5 -htp being converted into serotonin. As far as I’m aware when simply supplementing amino acids to improve neurotransmitter prevalence in the brain, tolerance will build very rapidly within a one week to two week period (from personal experience). Not saying it’s not viable to help out with mood when used sparingly, just saying there’s most likely better ways for continued treatment.”
The first study to show that Tβ4-promoted tissue repair was a dermal study performed in rats (Malinda et al., 1999). It had previously been found to promote angiogenesis and was reported to be high in platelets (Grant et al., 1995; Hannappel & van Kampen, 1987; Malinda, Goldstein, & Kleinman, 1997; Philp, Huff, Gho, Hannappel, & Kleinman, 2003). Since platelets are the first cells to enter a wound, it was clear that Tβ4 should be tested in dermal wounds in an animal model (Malinda et al., 1997, 1999; Philp, Badamchian, et al., 2003). In the first dermal study using 8 mm full-thickness punch wounds in rats, Tβ4 at 5 μg/50 μL of phosphate-buffered saline was found to accelerate wound closure, increase angiogenesis, and accelerate collagen deposition (Malinda et al., 1999). Tβ4 was only applied at the time of injury and at 48 h since after that the crust had formed. Visible macroscopic improvement was seen in the treated group by day 4. The study also found that Tβ4 promoted keratinocyte migration in vitro with activity in the picogram range. The findings were confirmed in various additional animal models (Table 1) and led to the clinical trials for hard to heal wound in patients as detailed in Table 2.
To untangle the ways different hormones together influence behavior in more naturalistic contexts, we worked with the Tsimane people in Bolivia. Traditional societies like the Tsimane are not living relics of the past, but their lifeways – small, tight-knit communities that produce their own food – can reveal the kinds of situations our hormone systems are well adapted to.
Differences among groups were analyzed using a one-way analysis of variance combined with the Bonferroni test. The relative intensities of mRNA and protein bands were assayed using Quantity-One software (Bio-Rad Co., Hercules, CA, USA); results were normalized to the mRNA and protein levels of beta-actin. All values were expressed as mean ± standard deviation. Differences were considered significant at p < 0.05.
Low oxytocin levels have been linked to autism and autistic spectrum disorders (e.g. Asperger syndrome) – a key element of these disorders being poor social functioning. Some scientists believe oxytocin could be used to treat these disorders. In addition, low oxytocin has been linked to depressive symptoms and it has been proposed as a treatment for depressive disorders. However, there is not enough evidence at present to support its use for any of these conditions.
5-HTP is sometimes taken by people coming down from MDMA to relieve post-MDMA dysphoria. As 5-HTP is a necessary precursor for the brain to produce more serotonin, and MDMA use depletes a person's natural serotonin levels, it is believed that taking 5-HTP after consuming MDMA will speed up serotonin production. DanceSafe claims that the anecdotal evidence is widespread and that the theory is physiologically reasonable. Backing up this approach is research conducted by Wang, et al. in 2007, which observed that MDMA-induced depletions of 5-HT (serotonin) were restored in rats after administration 5-HTP, and suggested that this approach might be clinically useful in abstinent MDMA users.